Research progress on the role mechanism of gut flora in postoperative delirium and its prevention strategy_West China Medical Journal

Authors：

LIU Xusheng ¹ , LIU Jianxiao ¹ , PENG Bo ¹ , YANG Yang ¹ , DU Nan ¹ , MA Wenxiang ¹ , XIE Jiajing ¹ ,  YU Yongjiang ^1,2

1. The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu 730000, P. R. China;
2. Department of Gastrointestinal Surgery / Hernia and Abdominal Wall Surgery, the First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P. R. China;

Corresponding author：

YU Yongjiang, Email: ylongy@163.com

Keywords：

Gut flora; postoperative delirium; review

DOI：

10.7507/1002-0179.202409119

Video：

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Abstract Full text Figures/Tables Video References Cited by

Postoperative delirium (POD) is a common postoperative complication. Dysregulation of gut flora is involved in POD through mechanisms such as neuroinflammation, oxidative stress, deposition of β-amyloid, and aberrant production of metabolites of gut flora. Therefore, interventions to regulate gut flora, such as probiotics, prebiotics, and faecal microbiota transplantation, can alleviate cognitive dysfunction. This article reviews the mechanisms of gut flora in POD and its prevention and treatment strategies, with the aim of providing new ideas for the clinical prevention and treatment of POD.

Citation： LIU Xusheng, LIU Jianxiao, PENG Bo, YANG Yang, DU Nan, MA Wenxiang, XIE Jiajing, YU Yongjiang. Research progress on the role mechanism of gut flora in postoperative delirium and its prevention strategy. West China Medical Journal, 2025, 40(4): 659-664. doi: 10.7507/1002-0179.202409119 Copy

1.	Jin Z, Hu J, Ma D. Postoperative delirium: perioperative assessment, risk reduction, and management. Br J Anaesth, 2020, 125(4): 492-504.
2.	Bellelli G, Brathwaite JS, Mazzola P. Delirium: a marker of vulnerability in older people. Front Aging Neurosci, 2021, 13: 626127.
3.	Subramaniyan S, Terrando N. Neuroinflammation and perioperative neurocognitive disorders. Anesth Analg, 2019, 128(4): 781-788.
4.	Zhang Y, Baldyga K, Dong Y, et al. The association between gut microbiota and postoperative delirium in patients. Transl Psychiatry, 2023, 13(1): 156.
5.	Zhang J, Bi JJ, Guo GJ, et al. Abnormal composition of gut microbiota contributes to delirium-like behaviors after abdominal surgery in mice. CNS Neurosci Ther, 2019, 25(6): 685-696.
6.	Liu H, Cheng G, Xu YL, et al. Preoperative status of gut microbiota predicts postoperative delirium in patients with gastric cancer. Front Psychiatry, 2022, 13: 852269.
7.	Yang L, Ding W, Dong Y, et al. Electroacupuncture attenuates surgical pain-induced delirium-like behavior in mice via remodeling gut microbiota and dendritic spine. Front Immunol, 2022, 13: 955581.
8.	Yang Z, Tong C, Qian X, et al. Mechanical bowel preparation is a risk factor for postoperative delirium as it alters the gut microbiota composition: a prospective randomized single-center study. Front Aging Neurosci, 2022, 14: 847610.
9.	Lu J, Hou W, Gao S, et al. The role of gut microbiota-gut-brain axis in perioperative neurocognitive dysfunction. Front Pharmacol, 2022, 13: 879745.
10.	Jiang XL, Gu XY, Zhou XX, et al. Intestinal dysbacteriosis mediates the reference memory deficit induced by anaesthesia/surgery in aged mice. Brain Behav Immun, 2019, 80: 605-615.
11.	Shin NR, Whon TW, Bae JW. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol, 2015, 33(9): 496-503.
12.	Dong L, Li J, Zhang C, et al. Gut microbiota: a new player in the pathogenesis of perioperative neurocognitive disorder?. Ibrain, 2021, 7(1): 37-43.
13.	Martin-Gallausiaux C, Marinelli L, Blottière HM, et al. SCFA: mechanisms and functional importance in the gut. Proc Nutr Soc, 2021, 80(1): 37-49.
14.	Li X, Wang G, He Y, et al. White-cell derived inflammatory biomarkers in prediction of postoperative delirium in elderly patients undergoing surgery for lower limb fracture under non-general anaesthesia. Clin Interv Aging, 2022, 17: 383-392.
15.	Roh JS, Sohn DH. Damage-associated molecular patterns in inflammatory diseases. Immune Netw, 2018, 18(4): e27.
16.	Ahmad MA, Kareem O, Khushtar M, et al. Neuroinflammation: a potential risk for dementia. Int J Mol Sci, 2022, 23(2): 616.
17.	Lederer AK, Pisarski P, Kousoulas L, et al. Postoperative changes of the microbiome: are surgical complications related to the gut flora? A systematic review. BMC Surg, 2017, 17(1): 125.
18.	Wen Y, Feng S, Dai H, et al. Intestinal dysbacteriosis-propelled T helper 17 cells activation mediate the perioperative neurocognitive disorder induced by anesthesia/surgery in aged rats. Neurosci Lett, 2022, 783: 136741.
19.	Pellegrini C, Antonioli L, Calderone V, et al. Microbiota-gut-brain axis in health and disease: is NLRP3 inflammasome at the crossroads of microbiota-gut-brain communications?. Prog Neurobiol, 2020, 191: 101806.
20.	Han S, Bian R, Chen Y, et al. Dysregulation of the gut microbiota contributes to sevoflurane-induced cognitive dysfunction in aged mice by activating the NLRP3 inflammasome. Mol Neurobiol, 2024, 61(12): 10500-10516.
21.	Safavynia SA, Goldstein PA. The role of neuroinflammation in postoperative cognitive dysfunction: moving from hypothesis to treatment. Front Psychiatry, 2018, 9: 752.
22.	Okonogi T, Kuga N, Yamakawa M, et al. Stress-induced vagal activity influences anxiety-relevant prefrontal and amygdala neuronal oscillations in male mice. Nat Commun, 2024, 15(1): 183.
23.	Sun Y, Wang X, Li L, et al. The role of gut microbiota in intestinal disease: from an oxidative stress perspective. Front Microbiol, 2024, 15: 1328324.
24.	Kunst C, Schmid S, Michalski M, et al. The influence of gut microbiota on oxidative stress and the immune system. Biomedicines, 2023, 11(5): 1388.
25.	Zhang J, Gao J, Guo G, et al. Anesthesia and surgery induce delirium-like behavior in susceptible mice: the role of oxidative stress. Am J Transl Res, 2018, 10(8): 2435-2444.
26.	Zuo CL, Wang CM, Liu J, et al. Isoflurane anesthesia in aged mice and effects of A1 adenosine receptors on cognitive impairment. CNS Neurosci Ther, 2018, 24(3): 212-221.
27.	Xie Z, Swain CA, Ward SA, et al. Preoperative cerebrospinal fluid β-amyloid/tau ratio and postoperative delirium. Ann Clin Transl Neurol, 2014, 1(5): 319-328.
28.	Zhang J, Zhu S, Jin P, et al. Graphene oxide improves postoperative cognitive dysfunction by maximally alleviating amyloid beta burden in mice. Theranostics, 2020, 10(26): 11908-11920.
29.	Kowalski K, Mulak A. Brain-gut-microbiota axis in Alzheimer’s disease. J Neurogastroenterol Motil, 2019, 25(1): 48-60.
30.	Cho JH, Chae CW, Lim JR, et al. Sodium butyrate ameliorates high glucose-suppressed neuronal mitophagy by restoring PRKN expression via inhibiting the RELA-HDAC8 complex. Autophagy, 2024, 20(7): 1505-1522.
31.	Liu X, Du ZR, Wang X, et al. Colonic dopaminergic neurons changed reversely with those in the midbrain via gut microbiota-mediated autophagy in a chronic Parkinson’s disease mice model. Front Aging Neurosci, 2021, 13: 649627.
32.	Dalile B, Van Oudenhove L, Vervliet B, et al. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol, 2019, 16(8): 461-478.
33.	Feng Y, Wang Y, Wang P, et al. Short-chain fatty acids manifest stimulative and protective effects on intestinal barrier function through the inhibition of NLRP3 inflammasome and autophagy. Cell Physiol Biochem, 2018, 49(1): 190-205.
34.	Brunt VE, LaRocca TJ, Bazzoni AE, et al. The gut microbiome-derived metabolite trimethylamine N-oxide modulates neuroinflammation and cognitive function with aging. Geroscience, 2021, 43(1): 377-394.
35.	Arrona Cardoza P, Spillane MB, Morales Marroquin E. Alzheimer’s disease and gut microbiota: does trimethylamine N-oxide (TMAO) play a role?. Nutr Rev, 2022, 80(2): 271-281.
36.	Lu X, Xue Z, Qian Y, et al. Changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm rats. Front Cell Infect Microbiol, 2022, 12: 945851.
37.	Moss DE. Improving anti-neurodegenerative benefits of acetylcholinesterase inhibitors in Alzheimer’s disease: are irreversible inhibitors the future?. Int J Mol Sci, 2020, 21(10): 3438.
38.	Yang X, Chen X. The crosstalk between the blood-brain barrier dysfunction and neuroinflammation after general anaesthesia. Curr Issues Mol Biol, 2022, 44(11): 5700-5717.
39.	Yang X, Yu D, Xue L, et al. Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice. Acta Pharm Sin B, 2020, 10(3): 475-487.
40.	Dodiya HB, Forsyth CB, Voigt RM, et al. Chronic stress-induced gut dysfunction exacerbates Parkinson’s disease phenotype and pathology in a rotenone-induced mouse model of Parkinson’s disease. Neurobiol Dis, 2020, 135: 104352.
41.	Liu F, Duan M, Fu H, et al. Orthopedic surgery causes gut microbiome dysbiosis and intestinal barrier dysfunction in prodromal alzheimer disease patients: a prospective observational cohort study. Ann Surg, 2022, 276(2): 270-280.
42.	Huang X, Hussain B, Chang J. Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms. CNS Neurosci Ther, 2021, 27(1): 36-47.
43.	Terrando N, Akassoglou K. Breaking barriers in postoperative delirium. Br J Anaesth, 2022, 129(2): 147-150.
44.	Minerbi A, Shen S. Gut microbiome in anesthesiology and pain medicine. Anesthesiology, 2022, 137(1): 93-108.
45.	Mao L, Zeng Q, Su W, et al. Elevation of miR-146a inhibits BTG2/BAX expression to ameliorate postoperative cognitive dysfunction following probiotics (VSL#3) Treatment. Mol Neurobiol, 2021, 58(7): 3457-3470.
46.	Liufu N, Liu L, Shen S, et al. Anesthesia and surgery induce age-dependent changes in behaviors and microbiota. Aging (Albany NY), 2020, 12(2): 1965-1986.
47.	Wang P, Yin X, Chen G, et al. Perioperative probiotic treatment decreased the incidence of postoperative cognitive impairment in elderly patients following non-cardiac surgery: a randomised double- blind and placebo-controlled trial. Clin Nutr, 2021, 40(1): 64-71.
48.	Yuan Q, Xin L, Han S, et al. Lactulose improves neurological outcomes by repressing harmful bacteria and regulating inflammatory reactions in mice after stroke. Front Cell Infect Microbiol, 2021, 11: 644448.
49.	Yang XD, Wang LK, Wu HY, et al. Effects of prebiotic galacto-oligosaccharide on postoperative cognitive dysfunction and neuroinflammation through targeting of the gut-brain axis. BMC Anesthesiol, 2018, 18(1): 177.
50.	Rao J, Qiao Y, Xie R, et al. Fecal microbiota transplantation ameliorates stress-induced depression-like behaviors associated with the inhibition of glial and NLRP3 inflammasome in rat brain. J Psychiatr Res, 2021, 137: 147-157.
51.	Cheng Y, Tan G, Zhu Q, et al. Efficacy of fecal microbiota transplantation in patients with Parkinson’s disease: clinical trial results from a randomized, placebo-controlled design. Gut microbes, 2023, 15(2): 2284247.
52.	Pan C, Zhang H, Zhang L, et al. Surgery-induced gut microbial dysbiosis promotes cognitive impairment via regulation of intestinal function and the metabolite palmitic amide. Microbiome, 2023, 11(1): 248.
53.	Lowe PP, Gyongyosi B, Satishchandran A, et al. Reduced gut microbiome protects from alcohol-induced neuroinflammation and alters intestinal and brain inflammasome expression. J Neuroinflammation, 2018, 15(1): 298.
54.	Liang P, Shan W, Zuo Z. Perioperative use of cefazolin ameliorates postoperative cognitive dysfunction but induces gut inflammation in mice. J Neuroinflammation, 2018, 15(1): 235.
55.	Luo A, Li S, Wang X, et al. Cefazolin improves anesthesia and surgery-induced cognitive impairments by modulating blood-brain barrier function, gut bacteria and short chain fatty acids. Front Aging Neurosci, 2021, 13: 748637.
56.	Wang G, Zhou H, Zhang L, et al. Effects of high-intensity interval training on gut microbiota profiles in 12 months’ old ICR mice. J Physiol Biochem, 2020, 76(4): 539-548.
57.	Zhu B, Zhou Y, Zhou W, et al. Electroacupuncture modulates gut microbiota in mice: a potential target in postoperative cognitive dysfunction. Anat Rec (Hoboken), 2023, 306(12): 3131-3143.
58.	Wang XQ, Li H, Li XN, et al. Gut-brain axis: possible role of gut microbiota in perioperative neurocognitive disorders. Front Aging Neurosci, 2021, 13: 745774.
59.	李增亮, 要旗, 张开元, 等. 肠道菌群在脓毒症发生发展中的作用及其治疗潜力. 医学新知, 2024, 34(12): 1417-1423.
60.	赵宇婷, 杨宇晨, 蔡智慧. 肠道菌群对乳腺癌化疗疗效及相关不良反应的影响概述. 药物流行病学杂志, 2025, 34(1): 94-98.

1. Jin Z, Hu J, Ma D. Postoperative delirium: perioperative assessment, risk reduction, and management. Br J Anaesth, 2020, 125(4): 492-504.
2. Bellelli G, Brathwaite JS, Mazzola P. Delirium: a marker of vulnerability in older people. Front Aging Neurosci, 2021, 13: 626127.
3. Subramaniyan S, Terrando N. Neuroinflammation and perioperative neurocognitive disorders. Anesth Analg, 2019, 128(4): 781-788.
4. Zhang Y, Baldyga K, Dong Y, et al. The association between gut microbiota and postoperative delirium in patients. Transl Psychiatry, 2023, 13(1): 156.
5. Zhang J, Bi JJ, Guo GJ, et al. Abnormal composition of gut microbiota contributes to delirium-like behaviors after abdominal surgery in mice. CNS Neurosci Ther, 2019, 25(6): 685-696.
6. Liu H, Cheng G, Xu YL, et al. Preoperative status of gut microbiota predicts postoperative delirium in patients with gastric cancer. Front Psychiatry, 2022, 13: 852269.
7. Yang L, Ding W, Dong Y, et al. Electroacupuncture attenuates surgical pain-induced delirium-like behavior in mice via remodeling gut microbiota and dendritic spine. Front Immunol, 2022, 13: 955581.
8. Yang Z, Tong C, Qian X, et al. Mechanical bowel preparation is a risk factor for postoperative delirium as it alters the gut microbiota composition: a prospective randomized single-center study. Front Aging Neurosci, 2022, 14: 847610.
9. Lu J, Hou W, Gao S, et al. The role of gut microbiota-gut-brain axis in perioperative neurocognitive dysfunction. Front Pharmacol, 2022, 13: 879745.
10. Jiang XL, Gu XY, Zhou XX, et al. Intestinal dysbacteriosis mediates the reference memory deficit induced by anaesthesia/surgery in aged mice. Brain Behav Immun, 2019, 80: 605-615.
11. Shin NR, Whon TW, Bae JW. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol, 2015, 33(9): 496-503.
12. Dong L, Li J, Zhang C, et al. Gut microbiota: a new player in the pathogenesis of perioperative neurocognitive disorder?. Ibrain, 2021, 7(1): 37-43.
13. Martin-Gallausiaux C, Marinelli L, Blottière HM, et al. SCFA: mechanisms and functional importance in the gut. Proc Nutr Soc, 2021, 80(1): 37-49.
14. Li X, Wang G, He Y, et al. White-cell derived inflammatory biomarkers in prediction of postoperative delirium in elderly patients undergoing surgery for lower limb fracture under non-general anaesthesia. Clin Interv Aging, 2022, 17: 383-392.
15. Roh JS, Sohn DH. Damage-associated molecular patterns in inflammatory diseases. Immune Netw, 2018, 18(4): e27.
16. Ahmad MA, Kareem O, Khushtar M, et al. Neuroinflammation: a potential risk for dementia. Int J Mol Sci, 2022, 23(2): 616.
17. Lederer AK, Pisarski P, Kousoulas L, et al. Postoperative changes of the microbiome: are surgical complications related to the gut flora? A systematic review. BMC Surg, 2017, 17(1): 125.
18. Wen Y, Feng S, Dai H, et al. Intestinal dysbacteriosis-propelled T helper 17 cells activation mediate the perioperative neurocognitive disorder induced by anesthesia/surgery in aged rats. Neurosci Lett, 2022, 783: 136741.
19. Pellegrini C, Antonioli L, Calderone V, et al. Microbiota-gut-brain axis in health and disease: is NLRP3 inflammasome at the crossroads of microbiota-gut-brain communications?. Prog Neurobiol, 2020, 191: 101806.
20. Han S, Bian R, Chen Y, et al. Dysregulation of the gut microbiota contributes to sevoflurane-induced cognitive dysfunction in aged mice by activating the NLRP3 inflammasome. Mol Neurobiol, 2024, 61(12): 10500-10516.
21. Safavynia SA, Goldstein PA. The role of neuroinflammation in postoperative cognitive dysfunction: moving from hypothesis to treatment. Front Psychiatry, 2018, 9: 752.
22. Okonogi T, Kuga N, Yamakawa M, et al. Stress-induced vagal activity influences anxiety-relevant prefrontal and amygdala neuronal oscillations in male mice. Nat Commun, 2024, 15(1): 183.
23. Sun Y, Wang X, Li L, et al. The role of gut microbiota in intestinal disease: from an oxidative stress perspective. Front Microbiol, 2024, 15: 1328324.
24. Kunst C, Schmid S, Michalski M, et al. The influence of gut microbiota on oxidative stress and the immune system. Biomedicines, 2023, 11(5): 1388.
25. Zhang J, Gao J, Guo G, et al. Anesthesia and surgery induce delirium-like behavior in susceptible mice: the role of oxidative stress. Am J Transl Res, 2018, 10(8): 2435-2444.
26. Zuo CL, Wang CM, Liu J, et al. Isoflurane anesthesia in aged mice and effects of A1 adenosine receptors on cognitive impairment. CNS Neurosci Ther, 2018, 24(3): 212-221.
27. Xie Z, Swain CA, Ward SA, et al. Preoperative cerebrospinal fluid β-amyloid/tau ratio and postoperative delirium. Ann Clin Transl Neurol, 2014, 1(5): 319-328.
28. Zhang J, Zhu S, Jin P, et al. Graphene oxide improves postoperative cognitive dysfunction by maximally alleviating amyloid beta burden in mice. Theranostics, 2020, 10(26): 11908-11920.
29. Kowalski K, Mulak A. Brain-gut-microbiota axis in Alzheimer’s disease. J Neurogastroenterol Motil, 2019, 25(1): 48-60.
30. Cho JH, Chae CW, Lim JR, et al. Sodium butyrate ameliorates high glucose-suppressed neuronal mitophagy by restoring PRKN expression via inhibiting the RELA-HDAC8 complex. Autophagy, 2024, 20(7): 1505-1522.
31. Liu X, Du ZR, Wang X, et al. Colonic dopaminergic neurons changed reversely with those in the midbrain via gut microbiota-mediated autophagy in a chronic Parkinson’s disease mice model. Front Aging Neurosci, 2021, 13: 649627.
32. Dalile B, Van Oudenhove L, Vervliet B, et al. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol, 2019, 16(8): 461-478.
33. Feng Y, Wang Y, Wang P, et al. Short-chain fatty acids manifest stimulative and protective effects on intestinal barrier function through the inhibition of NLRP3 inflammasome and autophagy. Cell Physiol Biochem, 2018, 49(1): 190-205.
34. Brunt VE, LaRocca TJ, Bazzoni AE, et al. The gut microbiome-derived metabolite trimethylamine N-oxide modulates neuroinflammation and cognitive function with aging. Geroscience, 2021, 43(1): 377-394.
35. Arrona Cardoza P, Spillane MB, Morales Marroquin E. Alzheimer’s disease and gut microbiota: does trimethylamine N-oxide (TMAO) play a role?. Nutr Rev, 2022, 80(2): 271-281.
36. Lu X, Xue Z, Qian Y, et al. Changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm rats. Front Cell Infect Microbiol, 2022, 12: 945851.
37. Moss DE. Improving anti-neurodegenerative benefits of acetylcholinesterase inhibitors in Alzheimer’s disease: are irreversible inhibitors the future?. Int J Mol Sci, 2020, 21(10): 3438.
38. Yang X, Chen X. The crosstalk between the blood-brain barrier dysfunction and neuroinflammation after general anaesthesia. Curr Issues Mol Biol, 2022, 44(11): 5700-5717.
39. Yang X, Yu D, Xue L, et al. Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice. Acta Pharm Sin B, 2020, 10(3): 475-487.
40. Dodiya HB, Forsyth CB, Voigt RM, et al. Chronic stress-induced gut dysfunction exacerbates Parkinson’s disease phenotype and pathology in a rotenone-induced mouse model of Parkinson’s disease. Neurobiol Dis, 2020, 135: 104352.
41. Liu F, Duan M, Fu H, et al. Orthopedic surgery causes gut microbiome dysbiosis and intestinal barrier dysfunction in prodromal alzheimer disease patients: a prospective observational cohort study. Ann Surg, 2022, 276(2): 270-280.
42. Huang X, Hussain B, Chang J. Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms. CNS Neurosci Ther, 2021, 27(1): 36-47.
43. Terrando N, Akassoglou K. Breaking barriers in postoperative delirium. Br J Anaesth, 2022, 129(2): 147-150.
44. Minerbi A, Shen S. Gut microbiome in anesthesiology and pain medicine. Anesthesiology, 2022, 137(1): 93-108.
45. Mao L, Zeng Q, Su W, et al. Elevation of miR-146a inhibits BTG2/BAX expression to ameliorate postoperative cognitive dysfunction following probiotics (VSL#3) Treatment. Mol Neurobiol, 2021, 58(7): 3457-3470.
46. Liufu N, Liu L, Shen S, et al. Anesthesia and surgery induce age-dependent changes in behaviors and microbiota. Aging (Albany NY), 2020, 12(2): 1965-1986.
47. Wang P, Yin X, Chen G, et al. Perioperative probiotic treatment decreased the incidence of postoperative cognitive impairment in elderly patients following non-cardiac surgery: a randomised double- blind and placebo-controlled trial. Clin Nutr, 2021, 40(1): 64-71.
48. Yuan Q, Xin L, Han S, et al. Lactulose improves neurological outcomes by repressing harmful bacteria and regulating inflammatory reactions in mice after stroke. Front Cell Infect Microbiol, 2021, 11: 644448.
49. Yang XD, Wang LK, Wu HY, et al. Effects of prebiotic galacto-oligosaccharide on postoperative cognitive dysfunction and neuroinflammation through targeting of the gut-brain axis. BMC Anesthesiol, 2018, 18(1): 177.
50. Rao J, Qiao Y, Xie R, et al. Fecal microbiota transplantation ameliorates stress-induced depression-like behaviors associated with the inhibition of glial and NLRP3 inflammasome in rat brain. J Psychiatr Res, 2021, 137: 147-157.
51. Cheng Y, Tan G, Zhu Q, et al. Efficacy of fecal microbiota transplantation in patients with Parkinson’s disease: clinical trial results from a randomized, placebo-controlled design. Gut microbes, 2023, 15(2): 2284247.
52. Pan C, Zhang H, Zhang L, et al. Surgery-induced gut microbial dysbiosis promotes cognitive impairment via regulation of intestinal function and the metabolite palmitic amide. Microbiome, 2023, 11(1): 248.
53. Lowe PP, Gyongyosi B, Satishchandran A, et al. Reduced gut microbiome protects from alcohol-induced neuroinflammation and alters intestinal and brain inflammasome expression. J Neuroinflammation, 2018, 15(1): 298.
54. Liang P, Shan W, Zuo Z. Perioperative use of cefazolin ameliorates postoperative cognitive dysfunction but induces gut inflammation in mice. J Neuroinflammation, 2018, 15(1): 235.
55. Luo A, Li S, Wang X, et al. Cefazolin improves anesthesia and surgery-induced cognitive impairments by modulating blood-brain barrier function, gut bacteria and short chain fatty acids. Front Aging Neurosci, 2021, 13: 748637.
56. Wang G, Zhou H, Zhang L, et al. Effects of high-intensity interval training on gut microbiota profiles in 12 months’ old ICR mice. J Physiol Biochem, 2020, 76(4): 539-548.
57. Zhu B, Zhou Y, Zhou W, et al. Electroacupuncture modulates gut microbiota in mice: a potential target in postoperative cognitive dysfunction. Anat Rec (Hoboken), 2023, 306(12): 3131-3143.
58. Wang XQ, Li H, Li XN, et al. Gut-brain axis: possible role of gut microbiota in perioperative neurocognitive disorders. Front Aging Neurosci, 2021, 13: 745774.
59. 李增亮, 要旗, 张开元, 等. 肠道菌群在脓毒症发生发展中的作用及其治疗潜力. 医学新知, 2024, 34(12): 1417-1423.
60. 赵宇婷, 杨宇晨, 蔡智慧. 肠道菌群对乳腺癌化疗疗效及相关不良反应的影响概述. 药物流行病学杂志, 2025, 34(1): 94-98.

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